Global metabolomic profiling targeting childhood obesity in the Hispanic population

Butte, Nancy F.; Yan, Lei; Zakeri, Issa; Mohney, Robert P.; Mehta, Nitesh R; Voruganti, V. Saroja; Göring, Harald H.H.; Cole, Shelley A.; Comuzzie, Anthony G.

doi:10.3945/ajcn.115.111872

Cited by 163 publications

(209 citation statements)

References 33 publications

(55 reference statements)

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“…ω-Oxidation is characterized by elevations in DCAC and is a known compensatory process in the setting of β-oxidative dysfunction (34). In obesity and diabetes, increased ω-oxidation has been reported in the setting of dysfunctional β-oxidation in OB mice and rats (35,36), and it has been demonstrated (as altered dicarboxylic metabolites) in limited human studies (37)(38)(39). Alterations in amino acid pools in the setting of incomplete β-oxidation may be found related to anaplerosis, a compensatory process of amino acid mobilization and oxidation to replenish the TCA cycle and maintain oxidative metabolism.…”

Section: Discussionmentioning

confidence: 99%

Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism

et al. 2017

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“…Furthermore, the ratio of 20: 3n-6 to 18: 2n-6, a marker for Δ6-desaturase activity, was also increased in obese children, while Δ5-desaturase activity was decreased [62,67] . In addition, several studies found 20: 3n-6 increased in obese children [62,63] , while the 18: 2n-6 was not affected [48] or decreased [62] .…”

Section: Childhoodmentioning

confidence: 97%

“…In general, phospholipids are decreased in the obese state [54,61] , but additionally the fatty acid composition is affected. Odd-chain fatty acids, like 17: 0 [52, [61][62][63] , or n-3 fatty acids [64,65] , like DHA, are decreased in obese subjects, while saturated fatty acids [65] , n-6 fatty acids [62], or 24: 1 [65] as well as 16: 1 and 17: 1 [48] are elevated. However, usually fatty acids can be related to dietary components.…”

Section: Childhoodmentioning

confidence: 99%

Early Programming of Obesity Throughout the Life Course: A Metabolomics Perspective

et al. 2017

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Background: Over the last decades, research on early life risk factors for obesity and its comorbidities in early life has gained attention within the field of developmental origins of health and diseases. Metabolomics studies that are trying to find early life biomarker and intervention targets for the early development of obesity and associated cardiovascular diseases could help break the inter-generational cycle of obesity. Summary: Metabolomics studies in the field of early programming are scarce and causality is lacking at this stage, as most of the studies are cross-sectional. The main metabolites in the focus of obesity are branched-chain and aromatic amino acids, long-chain polyunsaturated fatty acids, lysophosphatidylcholines, and sphingomyelins. Sex and puberty have not been considered in most of the biomarker studies, but show differences in the metabolite associations to obesity. Key Messages: There is still a lot unknown about the associations between early programming exposures, metabolite concentrations, and the development of obesity. The few studies focusing on this topic find similar metabolite classes in the same age groups being associated with rapid early growth or obesity; but due to differences in the methodological and statistical approaches, the single species often differ. Therefore, more research, preferably with standardized approaches, is needed.

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“…Metabolomics analyses in children have found that higher circulating branched chain amino acids (BCAAs) are associated with obesity status (10, 11), as well as subclinical risk factors for metabolic disease like insulin resistance (10, 12). Studies in adults have shown that elevations in serum branched chain amino acids (BCAAs) are detectable several years prior to development of insulin resistance and incident type 2 diabetes (13, 14), even among individuals of similar weight status (13).…”

Section: Introductionmentioning

confidence: 99%

Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva

et al. 2017

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Context Metabolomics has emerged as a powerful tool to characterize biomarkers and elucidate physiological processes underlying adverse health outcomes. Little is known of these relationships during gestation and infancy, which are critical period for development of metabolic disease risk. Objectives To identify cord blood metabolite patterns associated with birth size; and to investigate relations of the birth size-associated metabolite patterns, and a branched chain amino acid (BCAA) metabolite pattern with a range of newborn and perinatal characteristics. Methods Using untargeted mass-spectrometry, we quantified metabolites in cord blood of 126 mother-child pairs. After excluding 103 xenobiotics, we used principal components analysis (PCA) to consolidate the remaining 606 metabolites into principal components (“factors”). Next, we identified factors associated with gestational age-and sex-standardized birthweight z-score (BW/GA) and examined associations of the BW/GA-associated pattern(s) and the BCAA pattern with cord blood insulin, leptin, adiponectin, insulin-like growth factor (IGF)-1, IGF-2, and IGF binding protein 3 (IGFBP-3) using multivariable linear regression. Finally, we examined associations of maternal/perinatal characteristics with the cord blood metabolite patterns Results Mean BW/GA z-score was 0.27 ± 0.98 units. About half of the infants were male (52.4%) and white (57.1%). Of the 6 factors identified from PCA, one was associated with higher BW/GA: Factor 5, which comprised metabolites involved in energy production (malate, succinate, fumarate) and nucleotide turnover (inosine 5-monophosphate, adenosine 5-monophosphate, cytidine 5-monophosphate) pathways. In multivariable analysis, Factor 5 was related to higher cord blood leptin (1.64 [95% CI: 0.42, 2.87] ng/mL) and IGF-1 even after adjusting for IGFBP-3 (3.35 [0.25, 6.44] ng/mL). The BCAA pattern was associated with higher BW/GA (0.20 [0.03, 0.36] z-scores) and IGFBP-3 (106.5 [44.7, 168.2] ng/mL). No maternal characteristics were associated with either metabolite pattern; however, infants born via Cesarean delivery exhibited a higher score for Factor 5, and gestation length was inversely associated with the BCAA pattern. Conclusions Metabolites in energy production and DNA/RNA turnover pathways in cord blood are associated with larger size at birth, and higher leptin and IGF-1. Similarly, the BCAA pattern was associated with larger birth size and IGFBP-3.

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Global metabolomic profiling targeting childhood obesity in the Hispanic population

Cited by 163 publications

References 33 publications

Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism

Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism

Early Programming of Obesity Throughout the Life Course: A Metabolomics Perspective

Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva

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